Date Thesis Awarded


Access Type

Honors Thesis -- Access Restricted On-Campus Only

Degree Name

Bachelors of Science (BS)




Dr. Helen Murphy

Committee Members

Dr. Mark Forsyth

Dr. Kurt Williamson

Dr. Julie Agnew


Since the discovery of a neurodegenerative disease by Dr. Alois Alzheimer in 1907, the disease that bears his name has been a medical mystery. Even though the cause of this disease is still hotly debated, the pathology surrounding it has undergone extensive study and the clinical progression is well understood (1, 2). Alzheimer's Disease (AD) consists of multiple malfunctioning parts of the central nervous system, specifically within the brain. This pathological deterioration is connected to, but not exclusively caused by, the catastrophic effects of one protein: Amyloid-Beta Precursor Protein (APP).

There is some speculation that under normal conditions, APP works as a binding and signaling protein between neurons, but there is little experimental evidence to support this hypothesis (3). What is known about APP is related to its malfunctioning and its involvement in AD. Due to an incorrect cleavage of APP, an Amyloid-beta (A-beta) peptide is produced. This peptide then has the potential to become an A-beta prion triggering the progression of the disease. There have been studies that show strong evidence for A-beta being responsible for initiating the neural degeneration of AD (4). A prion is a misfolded version of a protein, compared to its wild-type cognate, that results in a protein with an infectious state: the contagious misfolded protein induces the same misfolded conformation in other proteins of the same type. We now know that among A-beta prions there are different strains, called conformers, that are distinguished by their “strength” or rate of reproduction (i.e., recruitment) (5, 6). The different conformers are associated with different disease pathologies and occur even with the same amino acid sequence (7). This creates prion subspecies that have the same genetic sequence but propagate different secondary structures.

Much of the basic research on prions has been conducted using the important biomedical research model organism Saccharomyces cerevisiae, or Baker’s yeast (8,9). This is the model system I use in this thesis because of our extensive understanding of its genetic makeup and fast generation time. The presence of native prions in S. cerevisiae is the most important reason for the use of this model organism. The natural yeast prion called [PSI+], which arises from a misfolded Sup35 protein (10), has a reporter system to easily track the fate of the prion. Previous research has demonstrated that the genetic material that encodes the first domain of SUP35, or region of the protein that allows it to misfold and aggregate, can be replaced with a coding region of the A-beta prion domain. This genetic manipulation allows for induction of the Alzheimer’s related, A-beta prion species inside the yeast cell (11). This ability for prion introduction and inducement allows for me to investigate A-beta prion species interactions associated with AD within a controlled experimental environment.

In this controlled environment, the conflict among different species vying for the same resources is a textbook set up for evolution to occur. This thesis attempts to look at that potential evolutionary competition between A-beta prion species and subspecies. By using two genetic alleles, Dutch and M1, we aimed to elucidate if and how competition occurs on the genetic level between alleles as well as the conformational level of subspecies within alleles. This study will hopefully shed light on the impact of prion evolution on disease pathology of AD.

This thesis will be broken up into two chapters. The first chapter is a literature review that aims to familiarize the reader with the original subject of this thesis: prion evolution. It is formatted to fit the structure of a Trends in Ecology and Evolution review article and serve as the main piece of scholarly work. The second chapter is focused on the project itself and is presented in a more traditional science article format. The make-up of this chapter, and thesis, will be more nontraditional due to disruption of lab experiments from the coronavirus pandemic. This chapter will demonstrate the work that had been done toward this thesis and analyze the data collected before the unexpected closure of laboratories. Due to lack of data, an overarching conclusion to the questions posed in this thesis will not be possible, but hopefully, Dr. Helen Murphy and her lab will be able to finish the experiments and come to a finite conclusion.

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Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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